Abstract：
Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P < 0.001), yielding positive predictive values of 100% and 90.9%, and negative predictive values of 82.4% and 86.4% at landmark and longitudinal time points, respectively. Patients with detectable MRD showed reduced disease-free survival (DFS) compared to those with undetectable MRD (P < 0.001). Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not (P = 0.05). To our knowledge, this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.
摘要：
在血浆样品中基因融合和MET改变是罕见且难以检测的。在具有这些突变的非小细胞肺癌（NSCLC）患者中，基于循环肿瘤DNA（ctDNA）的分子残留病（MRD）的临床检测效果仍然未知。这个未来,非干预性研究招募了49例具有可操作基因融合的可手术NSCLC患者(ALK，ROS1,RET,和FGFR1），MET外显子14跳跃或从头MET扩增。我们使用1021和338基因面板分析了43个肿瘤组织和111个连续围手术期血浆样本，分别。可检测的MRD与显著较高的复发率相关(P<0.001)。产生100%和90.9%的阳性预测值，在地标和纵向时间点的阴性预测值为82.4%和86.4%，分别。与未检测到MRD的患者相比，检测到MRD的患者无病生存期（DFS）降低（P<0.001）。与没有MRD的患者相比，在MRD中包含组织源性融合/MET改变的患者DFS降低（P=0.05）。据我们所知,这是关于ctDNA-MRD在有基因融合和MET改变的可手术NSCLC患者中临床检测疗效的第一项综合性研究.在术后MRD中具有可检测到的组织源性融合/MET改变的患者具有更差的临床结果。
